Biochemical and Biophysical Research Communications, Vol.440, No.1, 25-30, 2013
Mutant gamma PKC that causes spinocerebellar ataxia type 14 upregulates Hsp70, which protects cells from the mutant's cytotoxicity
Several missense mutations in the protein kinase C gamma (gamma PKC) gene have been found to cause spinocerebellar ataxia type 14 (SCA14), an autosomal dominant neurodegenerative disease. We previously demonstrated that the mutant gamma PKC found in SCA14 is misfolded, susceptible to aggregation and cytotoxic. Molecular chaperones assist the refolding and degradation of misfolded proteins and prevention of the proteins' aggregation. In the present study, we found that the expression of mutant gamma PKC-GFP increased the levels of heat-shock protein 70 (Hsp70) in SH-SY5Y cells. To elucidate the role of this elevation, we investigated the effect of siRNA-mediated knockdown of Hsp70 on the aggregation and cytotoxicity of mutant gamma PKC. Knockdown of Hsp70 exacerbated the aggregation and cytotoxicity of mutant gamma PKC-GFP by inhibiting this mutant's degradation. These findings suggest that mutant gamma PKC increases the level of Hsp70, which protects cells from the mutant's cytotoxicity by enhancing its degradation. (C) 2013 Elsevier Inc. All rights reserved.